ANTIGENIC DETERMINANTS OF VARICELLA VIRUS

水痘-带状疱疹病毒（VZV）是人类疱疹病毒， 常见的儿童疾病水痘的病原体， 再激活，皮节疹带状疱疹（带状疱疹）。 虽然 健康人只有中度痛苦，这两种疾病都很重要 儿童和青少年癌症发病和死亡的原因 或其他慢性疾病正在接受强化化疗， 骨髓/器官移植 由于VZV的严重后遗症 在免疫功能低下的患者中感染，NIH-NIAID目前是 赞助减毒活VZV的合作临床试验 疫苗 这项拨款提案的目标是定义和描述 VZV主要抗原决定簇。 VZV特异性糖蛋白将被 由于其他包膜病毒的研究， 表明糖基化抗原在免疫应答中起重要作用。 诱导保护性体液和细胞介导的免疫应答 感染的宿主;相同的糖蛋白也介导早期事件， 病毒与细胞相互作用。 具体目标包括： 以下研究：（1）产生鼠单克隆抗体组 实验室和疫苗VZV指定的糖蛋白抗体 （2）鉴定VZV前体和成熟体的糖基化成分 感染细胞和包膜病毒粒子的合成，（3）研究合成， 病毒糖蛋白的加工和细胞内转运，（4） 分离和纯化单个病毒糖蛋白， 蛋白质和糖部分的结构分析，和（5）相关 生物功能，例如，抗体依赖性细胞介导的中和 细胞毒性和迟发型超敏反应及其决定因素 单个糖蛋白。 技术将包括放射免疫 沉淀，SDS-PAGE，免疫印迹，亲和和高效 液相色谱，胰蛋白酶肽图，生物凝胶过滤 糖肽、碳水化合物的甲基化分析和免疫电子 显微镜 因此，这项研究项目将研究生物学， VZV糖蛋白的生物化学和免疫生物化学。 在 一个合作研究的奋进，结构基因编码的 单个病毒糖蛋白将通过重组DNA技术作图。

Varicella-zoster virus (VZV) is the human herpesvirus which is the etiologic agent of both the common childhood illness chickenpox and, upon reactivation, the dermatomal exanthem shingles (herpes zoster). Although only moderately distressful in healthy people, both diseases are important causes of morbidity and mortality in children and young adults with cancer or other chronic illnesses being treated with intensive chemotherapy or bone marrow/organ transplantation. Because of the serious sequelae of VZV infection in immunocompromised patients, the NIH-NIAID is currently sponsoring a collaborative clinical trial of a live attenuated VZV vaccine. The goal of this grant proposal is to define and characterize major VZV antigenic determinants. Glycoproteins specified by VZV will be given the highest priority since studies of other enveloped viruses demonstrate that glycosylated antigens play an important role in the induction of protective humoral and cell-mediated immune responses by the infected host; the same glycoproteins also mediate early events in the interaction between virus and cell. The specific aims include the following investigations: (1) produce panels of murine monoclonal antibodies to glycoproteins specified by a laboratory and a vaccine VZV strain, (2) identify the precursor and mature VZV glycosylated constituents of the infected cell and the enveloped virion, (3) study the synthesis, processing and intracellular transport of the viral glycoproteins, (4) isolate and purify the individual viral glycoproteins and perform structural analysis of the protein and sugar moieties, and (5) correlate biologic functions, e.g., neutralization, antibody dependent cell mediated cytotoxicity and delayed type hypersensitivity with determinants on individual glycoproteins. Techniques will include radioimmune precipitation, SDS-PAGE, immunoblotting, affinity and high performance liquid chromatography, tryptic peptide mapping, Bio-Gel filtration of glycopeptides, methylation analyses of carbohydrates and immunoelectron microscopy. This research project, therefore, will examine the biology, the biochemistry, and the immunobiochemistry of the VZV glycoproteins. In a collaborative research endeavor, the structural genes which encode the individual viral glycoproteins will be mapped by recombinant DNA technology.